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Liver Targeting Albumin-Coated Silybin-Phospholipid Particles Prepared by Nab™ Technology for Improving Treatment Effect of Acute Liver Damage in Intravenous Administration

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Abstract

In this study, a novel human serum albumin nanoparticle loading silybin-phospholipid complex (SLNPs) was developed for liver targeting after intravenous administration. The preparation of the drug delivery system consisted of two steps; initially, a silybin-phospholipid complex (SLC) was produced to improve the lipophilicity of SLB to then achieve enhanced encapsulation of SLB in albumin nanoparticles. FT-IR and XRD analysis confirmed the successful formation of SLC. The complex ratio of SLC in the first step was 99.6%. The encapsulation efficiency and drug loading of SLNPs in the second step were 96.2% and 5.6%, respectively. SLNPs were spherical and well-dispersed, with a zeta potential of approximately − 10 mV, and a mean particle size around 200 nm. An in vivo tissue distribution experiment and a pharmacodynamic experiment showed that, compared with SLB solution, SLNPs had an improved SLB accumulation in the liver. The hepatoprotective effect of SLNPs on CCl4-induced acute liver damage was evaluated. CCl4-damaged mice showed an increased enzymatic activity of ALT and AST; however, enzyme levels returned to near-normal levels in high-dose SLNP-treated mice. As SLNPs combine the enhanced oil solubility of SLC and the passive targeting of albumin nanoparticles, they possess great potential for the treatment of acute liver damage.

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Acknowledgments

Amanda Pearce is sincerely thanked for correcting the manuscript. The authors alone are responsible for the content and writing of this article.

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Correspondence to Haibing He.

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Lu, C., Li, X., Liang, X. et al. Liver Targeting Albumin-Coated Silybin-Phospholipid Particles Prepared by Nab™ Technology for Improving Treatment Effect of Acute Liver Damage in Intravenous Administration. AAPS PharmSciTech 20, 293 (2019). https://doi.org/10.1208/s12249-019-1504-y

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KEY WORDS

  • acute liver damage
  • silybin-phospholipid complex
  • SLNPs
  • liver targeting
  • intravenous administration